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Neurobiol Dis. 2019 Apr;124:263-275. doi: 10.1016/j.nbd.2018.11.021. Epub 2018 Nov 22.

Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS.

Author information

1
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna 148, 10154 Turin, TO, Italy.
2
Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, TO, Italy.
3
Laboratorio di Ingegneria del Sistema Neuromuscolare (LISIN), Politecnico di Torino, Corso Castelfidardo 42/a, 10138 Turin, TO, Italy.
4
NeuroMuscularFunction research group, School of Exercise and Sport Sciences, Department of Medical Sciences, University of Turin, Piazza Gian Lorenzo Bernini, 12, 10143 Turin, TO, Italy.
5
Milan Unit, Istituto di Ricerca Genetica e Biomedica, CNR, Via Fantoli 16/15, 20138 Milan, MI, Italy; Humanitas Clinical and Research Center, via Manzoni 56, 20089 Rozzano, MI, Italy.
6
Istituto di Genetica Molecolare, CNR, Via Abbiategrasso 207, 27100 Pavia, PV, Italy.
7
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa, 19, 20156 Milano, MI, Italy.
8
Avantea, Via Porcellasco 7F, 26100 Cremona, CR, Italy; Fondazione Avantea, Via Porcellasco 7F, 26100 Cremona, CR, Italy.
9
Avantea, Via Porcellasco 7F, 26100 Cremona, CR, Italy.
10
Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Department of Neuroscience, Regione Gonzole 10, 10043 Orbassano, TO, Italy.
11
Department of Neuroradiology, A.O.U. Città della Salute e della Scienza, Corso Bramante 88, 10126 Turin, TO, Italy.
12
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna 148, 10154 Turin, TO, Italy. Electronic address: cristiano.corona@izsto.it.

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a neural disorder gradually leading to paralysis of the whole body. Alterations in superoxide dismutase SOD1 gene have been linked with several variants of familial ALS. Here, we investigated a transgenic (Tg) cloned swine model expressing the human pathological hSOD1G93A allele. As in patients, these Tg pigs transmitted the disease to the progeny with an autosomal dominant trait and showed ALS onset from about 27 months of age. Post mortem analysis revealed motor neuron (MN) degeneration, gliosis and hSOD1 protein aggregates in brainstem and spinal cord. Severe skeletal muscle pathology including necrosis and inflammation was observed at the end stage, as well. Remarkably, as in human patients, these Tg pigs showed a quite long presymptomatic phase in which gradually increasing amounts of TDP-43 were detected in peripheral blood mononuclear cells. Thus, this transgenic swine model opens the unique opportunity to investigate ALS biomarkers even before disease onset other than testing novel drugs and possible medical devices.

KEYWORDS:

ALS; Amyotrophic lateral sclerosis; SOD1; TDP-43; Transgenic pig

PMID:
30471417
DOI:
10.1016/j.nbd.2018.11.021
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